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1.
Plant Commun ; 5(4): 100814, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38213026

RESUMEN

Ambient temperature affects flowering time in plants, and the MADS-box transcription factor SHORT VEGETATIVE PHASE (SVP) plays a crucial role in the response to changes in ambient temperature. SVP protein stability is regulated by the 26S proteasome pathway and decreases at high ambient temperature, but the details of SVP degradation are unclear. Here, we show that SVP degradation at high ambient temperature is mediated by the CULLIN3-RING E3 ubiquitin ligase (CRL3) complex in Arabidopsis thaliana. We identified a previously uncharacterized protein that interacts with SVP at high ambient temperature and contains a BTB/POZ domain. We named this protein LATE FLOWERING AT HIGH TEMPERATURE 1 (LFH1). Single mutants of LFH1 or CULLIN3A (CUL3A) showed late flowering specifically at 27°C. LFH1 protein levels increased at high ambient temperature. We found that LFH1 interacts with CUL3A in the cytoplasm and is important for SVP-CUL3A complex formation. Mutations in CUL3A and/or LFH1 led to increased SVP protein stability at high ambient temperature, suggesting that the CUL3-LFH1 complex functions in SVP degradation. Screening E2 ubiquitin-conjugating enzymes (UBCs) using RING-BOX PROTEIN 1 (RBX1), a component of the CRL3 complex, as bait identified UBC15. ubc15 mutants also showed late flowering at high ambient temperature. In vitro and in vivo ubiquitination assays using recombinant CUL3A, LFH1, RBX1, and UBC15 showed that SVP is highly ubiquitinated in an ATP-dependent manner. Collectively, these results indicate that the degradation of SVP at high ambient temperature is mediated by a CRL3 complex comprising CUL3A, LFH1, and UBC15.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ubiquitina-Proteína Ligasas , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ligasas/metabolismo , Temperatura , Ubiquitinas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
3.
Asian Biomed (Res Rev News) ; 17(1): 39-42, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37706054

RESUMEN

Background: The urine immunochromatographic assay is a useful screening tool for patients suspected of acute drug intoxication in emergency conditions. Diphenhydramine intoxication shows symptoms similar to those of tricyclic antidepressant (TCA) intoxication. Case presentation: We examined a case of diphenhydramine intoxication showing cerebellar ataxia and prolonged false positive results for TCA in the urine. The urine TCA test showed persistently positive results even 60 h after the patient's initial drug screening. We observed negative conversion 90 h after the initial drug screening. Discussion: Considering the similarities of clinical symptoms between diphenhydramine and TCA intoxication, emergency physicians should consider the possibility of cross-reactivity in the diagnosis of a patient with unknown acute drug intoxication showing positive results of TCA immunochromatographic assay in the urine. Conclusion: The present case suggests that diphenhydramine overdose may cause cerebellar ataxia and show prolonged cross-reactivity as TCA in the urine.

4.
Proc Natl Acad Sci U S A ; 120(33): e2300036120, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37549292

RESUMEN

While the world is rapidly transforming into a superaging society, pharmaceutical approaches to treat sarcopenia have hitherto not been successful due to their insufficient efficacy and failure to specifically target skeletal muscle cells (skMCs). Although electrical stimulation (ES) is emerging as an alternative intervention, its efficacy toward treating sarcopenia remains unexplored. In this study, we demonstrate a silver electroceutical technology with the potential to treat sarcopenia. First, we developed a high-throughput ES screening platform that can simultaneously stimulate 15 independent conditions, while utilizing only a small number of human-derived primary aged/young skMCs (hAskMC/hYskMC). The in vitro screening showed that specific ES conditions induced hypertrophy and rejuvenation in hAskMCs, and the optimal ES frequency in hAskMCs was different from that in hYskMCs. When applied to aged mice in vivo, specific ES conditions improved the prevalence and thickness of Type IIA fibers, along with biomechanical attributes, toward a younger skMC phenotype. This study is expected to pave the way toward an electroceutical treatment for sarcopenia with minimal side effects and help realize personalized bioelectronic medicine.


Asunto(s)
Sarcopenia , Animales , Humanos , Ratones , Fibras Musculares Esqueléticas , Músculo Esquelético/fisiología , Fenotipo , Sarcopenia/terapia , Plata
5.
Anal Chem ; 95(26): 9949-9958, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37279022

RESUMEN

Natural killer (NK) cells are a part of the innate immune system, providing the first line of defense against cancer cells and pathogens at an early stage. Hence, they are attracting attention as a valuable resource for allogeneic cell immunotherapy. However, NK cells exist with limited proportion in blood, and obtaining sufficient clinical-grade NK cells with highly viable and minimal stress is critical for successful immune cell therapy. Conventional purification methods via immunoaffinity or density gradient centrifugation had several limitations in yield, purity, and cellular stress, which might cause an increased risk for graft versus host disease and reduced efficacy due to NK cell malfunction, exhaustion, and apoptosis. Moreover, reducing the variations of isolation performance caused by the manual process is another unmet need for uniform quality of the living drug. Here, an automated system using an NK disc (NKD) based on continuous centrifugal microfluidics (CCM) technology was developed to isolate NK cells from whole blood with high yield, purity, reproducibility, and low stress. The CCM technology, which operates fluidic manipulation under disc rotation, enabled precise extraction of the ultra-thin target fluid layer generated by blood centrifugation. Compared to the conventional manual method, the CCM-NKD isolated NK cells with higher yield (recovery rate) and purity, while maintaining better reproducibility. Furthermore, since the CCM-NKD maintained substantially milder centrifugation conditions (120 ×g for 10 min) compared to the conventional approach (1200 ×g for 20 min), it showed reduced cellular stress and increased antioxidant capacity in the isolated NK cells. Based on the results, the CCM-NKD is expected to be a useful tool to provide highly intact and viable cell weapons for successful immune cell therapy.


Asunto(s)
Células Asesinas Naturales , Microfluídica , Reproducibilidad de los Resultados , Inmunoterapia
6.
Theranostics ; 13(5): 1506-1519, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37056568

RESUMEN

Natural killer (NK) cells are an attractive cell source in cancer immunotherapy due to their potent antitumor ability and promising safety for allogenic applications. However, the clinical outcome of NK cell therapy has been limited due to poor persistence and loss of activity in the cytokine-deficient tumor microenvironment. Benefits from exogenous administration of soluble interleukin-2 (IL-2) to stimulate the activity of NK cells have not been significant due to cytokine consumption and activation of other immune cells, compromising both efficacy and safety. Methods: To overcome these drawbacks, we developed a novel membrane-bound protein (MBP) technology to express IL-2 on the surface of NK-92 cells (MBP NK) inducing autocrine signal for proliferation without IL-2 supplementation. Results: The MBP NK cells exhibited not only improved proliferation in IL-2 deficient conditions but also stronger secretion of cytolytic granules leading to enhanced anti-tumor activity both in vitro and in vivo. Furthermore, the experiment with a spheroid solid tumor model exhibited enhanced infiltration by MBP NK cells creating higher local effector-to-target ratio for efficient tumor killing. These results suggest MBP technology can be an effective utility for NK-92 cell engineering to increase anti-tumor activity and reduce potential adverse effects, providing a higher therapeutic index in clinical applications.


Asunto(s)
Citocinas , Interleucina-2 , Citocinas/metabolismo , Interleucina-2/metabolismo , Línea Celular Tumoral , Células Asesinas Naturales , Inmunoterapia Adoptiva/métodos
7.
Int J Biol Macromol ; 234: 123685, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36796554

RESUMEN

Interests in the development and exploration of industrial applications of medicinal mushrooms as postbiotics have lately increased. We recently reported the potential use of Phellinus linteus mycelial-containing whole culture extract (PLME) prepared by submerged cultivation as a postbiotic that promotes immune system activation. Here, we aimed to isolate and structurally elucidate the active ingredients in PLME by activity-guided fractionation. The intestinal immunostimulatory activity was evaluated by bone marrow (BM) cell proliferation activity and related cytokine production in C3H-HeN mouse-derived Peyer's patch (PP) cells treated with polysaccharide fractions. The initially crude polysaccharide (PLME-CP) of PLME prepared using ethanol precipitation was further fractionated into four fractions (PLME-CP-0 to -III) by anion-exchange column chromatography. BM cell proliferation and cytokine production of PLME-CP-III were significantly improved compared to those of PLME-CP. PLME-CP-III was then fractionated into PLME-CP-III-1 and PLME-CP-III-2 by gel filtration chromatography. Based on the molecular weight distribution, monosaccharide, and glycosyl linkage analyses, PLME-CP-III-1 was revealed as a novel galacturonic acid-rich acidic polysaccharide and further shown to play an important role in facilitating PP-mediated intestinal immunostimulatory activity. This is the first study demonstrating the structural characteristics of a novel intestinal immune system modulating acidic polysaccharide from P. linteus mycelium-containing whole culture broth postbiotics.


Asunto(s)
Sistema Inmunológico , Polisacáridos , Animales , Ratones , Ratones Endogámicos C3H , Polisacáridos/química , Citocinas
8.
Biosens Bioelectron ; 224: 115055, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36630746

RESUMEN

Charcot-Marie-Tooth disease subtype 1A (CMT1A) is one of the most prevalent demyelinating peripheral neuropathies worldwide, caused by duplication of the peripheral myelin protein 22 (PMP22) gene, which is expressed primarily in Schwann cells (SCs). PMP22 overexpression in SCs leads to intracellular aggregation of the protein, which eventually results in demyelination. Unfortunately, previous biochemical approaches have not resulted in an approved treatment for CMT1A disease, compelling the pursuit for a biophysical approach such as electrical stimulation (ES). However, the effects of ES on CMT1A SCs have remained unexplored. In this study, we established PMP22-overexpressed Schwannoma cells as a CMT1A in vitro model, and investigated the biomolecular changes upon applying ES via a custom-made high-throughput ES platform, screening for the condition that delivers optimal therapeutic effects. While PMP22-overexpressed Schwannoma exhibited intracellular PMP22 aggregation, ES at 20 Hz for 1 h improved this phenomenon, bringing PMP22 distribution closer to healthy condition. ES at this condition also enhanced the expression of the genes encoding myelin basic protein (MBP) and myelin-associated glycoprotein (MAG), which are essential for assembling myelin sheath. Furthermore, ES altered the gene expression for myelination-regulating transcription factors Krox-20, Oct-6, c-Jun and Sox10, inducing pro-myelinating effects in PMP22-overexpressed Schwannoma. While electroceuticals has previously been applied in the peripheral nervous system towards acquired peripheral neuropathies such as pain and nerve injury, this study demonstrates its effectiveness towards ameliorating biomolecular abnormalities in an in vitro model of CMT1A, an inherited peripheral neuropathy. These findings will facilitate the clinical translation of an electroceutical treatment for CMT1A.


Asunto(s)
Técnicas Biosensibles , Enfermedad de Charcot-Marie-Tooth , Neurilemoma , Humanos , Proteínas de la Mielina/genética , Proteínas de la Mielina/metabolismo , Vaina de Mielina/genética , Vaina de Mielina/metabolismo , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Neurilemoma/metabolismo
9.
J Integr Plant Biol ; 65(5): 1226-1240, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36511120

RESUMEN

RAV1 (Related to ABI3/VP1) is a plant-specific B3 and AP2 domain-containing transcription factor that acts as a negative regulator of growth in many plant species. The expression of RAV1 is downregulated by brassinosteroids (BRs); large-scale transcriptome analyses have shown that the expression of RAV1 was previously targeted by BRI1-EMS-SUPPRESOR1 (BES1) and BRASSINAZOLE-RESISTANT1 (BZR1), which are critical transcription factors for the BR-signaling process. Using RAV1-overexpressing transgenic plants, we showed that RAV1 overexpression reduced the BR signaling capacity, resulting in the downregulation of BR biosynthetic genes and BES1 expression. Furthermore, we demonstrated that BES1, not BZR1, is directly bound to the RAV1 promoter and repressed RAV1 expression, and vice versa; RAV1 is also bound to the BES1 promoter and repressed BES1 expression. This mutual inhibition was specific to RAV1 and BES1 because RAV1 exhibited binding activity to the BZR1 promoter but did not repress BZR1 expression. We observed that constitutively activated BR signaling phenotypes in bes1-D were attenuated by the repression of endogenous BES1 expression in transgenic bes1-D plants overexpressing RAV1. RNA-sequencing analysis of RAV1-overexpressing transgenic plants and bes1-D mutant plants revealed differentially expressed genes by RAV1 and BES1 and genes that were oppositely co-regulated by RAV1 and BES1. RAV1 and BES1 regulated different transcriptomes but co-regulated a specific set of genes responsible for the balance between growth and defense. These results suggested that the mutual inhibitory transcriptional activities of RAV1 and BES1 provide fine regulatory mechanisms for plant growth and development.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brasinoesteroides/farmacología , Brasinoesteroides/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Desarrollo de la Planta , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
10.
Antioxidants (Basel) ; 11(12)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36552691

RESUMEN

Oxidative stress and the inflammatory response are known to be the most important pathological factors for aging skin cells. Therefore, substances that protect skin cells from oxidative stress and inflammatory reactions of the skin have potential as functional ingredients for skin care. In the present study, we investigated the potential of Sargassum macrocarpum as an anti-inflammatory candidate for inflammatory skin disease. Antioxidant and anti-inflammatory activities are desirable properties in such functional materials. The total polyphenol content as well as antioxidant and anti-inflammatory activities were evaluated in hot-water (HES) and ethanol (EES) extracts of S. macrocarpum. The polyphenol content was higher in the HES (HES: 115.9 ± 15.3 mg GA/g, EES: 3.9 ± 0.5 mg GA/g), and the HES also had ABTS (HES: IC50 1.0 ± 0.0 mg/mL, EES: IC50 16.09 ± 0.7 mg/mL) and DPPH (HES: IC50 6.50 ± 0.3 mg/mL, EES: IC50 35.3 ± 3.1 mg/mL) radical scavenging capacities as well as FRAP activity (HES: IC50 18.8 ± 0.4 mg/mL, EES: IC50 n.d.). Compared with the EES at the equivalent concentration range (1.25-20 µg/mL), the HES exerted a more potent inhibitory activity on LPS-stimulated nitric oxide (10.3-43.1%), IL-6 (15.7-45.0%), and TNF-α (14.1-20.8%) in RAW 264.7 macrophage cells in addition to TNF-α and IFN-γ-facilitated IL-6 (10.9-84.1%) and IL-8 (7.7-73.2%) in HaCaT keratinocytes. These results suggested that water-soluble materials might be deeply involved in the antioxidant and anti-inflammatory activity in S. macrocarpum. General composition analysis indicated that the HES contains more carbohydrates and polyphenols than the EES, and the monosaccharide composition analysis suggested that fucose-containing sulfated polysaccharide and ß-glucan might be potent anti-inflammatory candidates in the HES. The present study presents important preliminary results and a valuable strategy for developing novel anti-skin dermatitis candidates using a hot-water extract of S. macrocarpum.

11.
Pharmaceuticals (Basel) ; 15(10)2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-36297326

RESUMEN

Medicinal mushrooms are an important natural resource promoting health benefits. Herein, Phellinus linteus mycelia were prepared under submerged cultivation, the mycelium-containing culture broth was extracted as a whole to obtain the postbiotic materials (PLME), and its effect on the immune system was evaluated in normal C3H/HeN mice. Oral administration of PLME for 4 weeks was well tolerated and safe. In the PLME-administered groups, in addition to the production of immunostimulatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), the mitogenic activity was significantly increased. PLME administration also significantly increased the levels of serum immunoglobulin G (IgG) and IgA in the small intestinal fluid and Peyer's patches and enhanced Peyer's patch-mediated bone marrow cell proliferation activity and cytokine production (IL-2, IL-6, and IFN-γ). Histomorphometric analyses showed an increase in immune cells in the spleen and small intestinal tissues of mice administered PLME, supporting the rationale for its immune system activation. PLME mainly contained neutral sugar (969.1 mg/g), comprising primarily of glucose as a monosaccharide unit. The ß-glucan content was 88.5 mg/g. Data suggest that PLME effectively promote immune function by stimulating the systemic immune system through the spleen and intestinal immune tissues. PLME can thus be developed as a functional ingredient to enhance immune functions.

12.
Adv Sci (Weinh) ; 9(32): e2201358, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35975427

RESUMEN

Although many efforts are undertaken to treat peripheral demyelinating neuropathies based on biochemical interventions, unfortunately, there is no approved treatment yet. Furthermore, previous studies have not shown improvement of the myelin membrane at the biomolecular level. Here, an electroceutical treatment is introduced as a biophysical intervention to treat Charcot-Marie-Tooth (CMT) disease-the most prevalent peripheral demyelinating neuropathy worldwide-using a mouse model. The specific electrical stimulation (ES) condition (50 mV mm-1 , 20 Hz, 1 h) for optimal myelination is found via an in vitro ES screening system, and its promyelinating effect is validated with ex vivo dorsal root ganglion model. Biomolecular investigation via time-of-flight secondary ion mass spectrometry shows that ES ameliorates distribution abnormalities of peripheral myelin protein 22 and cholesterol in the myelin membrane, revealing the restoration of myelin membrane integrity. ES intervention in vivo via flexible implantable electrodes shows not only gradual rehabilitation of mouse behavioral phenotypes (balance and endurance), but also restored myelin thickness, compactness, and membrane integrity. This study demonstrates, for the first time, that an electroceutical approach with the optimal ES condition has the potential to treat CMT disease and restore impaired myelin membrane integrity, shifting the paradigm toward practical interventions for peripheral demyelinating neuropathies.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Enfermedades Desmielinizantes , Animales , Enfermedad de Charcot-Marie-Tooth/terapia , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Enfermedades Desmielinizantes/terapia , Enfermedades Desmielinizantes/genética , Vaina de Mielina/metabolismo , Modelos Animales de Enfermedad , Proteínas
13.
Lab Chip ; 22(17): 3268-3276, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35916196

RESUMEN

Progress in neurological research has experienced bottlenecks owing to the limited availability of purified primary neurons. Since neuronal cells are non-proliferative, it is necessary to obtain purified neurons from animal models or human patients for experimental work. However, currently available methods for purifying primary neurons are time-consuming (taking approximately 1 week), and suffer from insufficient viability and purity. Here, we report a method for rapid enrichment of neurons from the mouse embryonic dorsal root ganglion (DRG), using a fully-automated continuous centrifugal microfluidics (CCM) based neuron purification disc (NPD). Non-neuronal cells were removed via negative depletion by combining density gradient centrifugation and immunomagnetic separation. The CCM-NPD platform enables effective isolation of intact neurons within 13 min, which is approximately 800 times faster than the conventional chemical purification method. Furthermore, the neurons purified using the CCM-NPD platform showed better neurite growth, along with higher viability (93.5%) and purity (97.0%) after 1 week of culture, compared to the chemical purification method. Therefore, the proposed automated and rapid system yields purified DRG neurons with high viability and purity, while avoiding the use of harsh chemicals. We believe this system will significantly mitigate the shortage of purified primary neurons and advance neurological research.


Asunto(s)
Ganglios Espinales , Microfluídica , Animales , Separación Celular/métodos , Células Cultivadas , Humanos , Separación Inmunomagnética , Ratones , Neuronas
14.
Ideggyogy Sz ; 75(7-08): 279-283, 2022 Jul 30.
Artículo en Húngaro | MEDLINE | ID: mdl-35916615

RESUMEN

The blink reflex test of the trigeminal nerve can provide valuable information about lesions site. However it may not find small compressive lesions. We observed peak latency prolongation of the blink reflex test in a patient with trigeminal neuralgia caused by a small Meckel's cave mass, in whom the onset latency was normal. Conclusion - We suggest peak latency of the blink reflex might be a valuable aid for discerning small mass in patients with trigeminal neuralgia. This is the first case report of compressive trigeminal neuralgia showing peak latency prolongation of the blink reflex test.


Asunto(s)
Neuralgia del Trigémino , Parpadeo , Humanos , Nervio Trigémino/patología , Neuralgia del Trigémino/etiología , Neuralgia del Trigémino/patología
15.
Theranostics ; 12(8): 3676-3689, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35664056

RESUMEN

Understanding cancer heterogeneity is essential to finding diverse genetic mutations in metastatic cancers. Thus, it is critical to isolate all types of CTCs to identify accurate cancer information from patients. Moreover, full automation robustly capturing the full spectrum of CTCs is an urgent need for CTC diagnosis to be routine clinical practice. Methods: Here we report the full capture of heterogeneous CTC populations using fully automated, negative depletion-based continuous centrifugal microfluidics (CCM). Results: The CCM system demonstrated high performance (recovery rates exceeding 90% and WBC depletion rate of 99.9%) across a wide range of phenotypes (EpCAM(+), EpCAM(-), small-, large-sized, and cluster) and cancers (lung, breast, and bladder). Applied in 30 lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR) mutations, the system isolated diverse phenotypes of CTCs in marker expression and size, implying the importance of unbiased isolation. Genetic analyses of intra-patient samples comparing cell-free DNA with CCM-isolated CTCs yielded perfect concordance, and CTC enumeration using our technique was correlated with clinical progression as well as response to EGFR inhibitors. Conclusion: Our system also introduces technical advances which assure rapid, reliable, and reproducible results, thus enabling a more comprehensive application of robust CTC analysis in clinical practice.


Asunto(s)
Células Neoplásicas Circulantes , Automatización , Línea Celular Tumoral , Separación Celular/métodos , Molécula de Adhesión Celular Epitelial/genética , Receptores ErbB/genética , Humanos , Microfluídica/métodos , Células Neoplásicas Circulantes/metabolismo
16.
J Sci Food Agric ; 102(7): 2846-2854, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34741313

RESUMEN

BACKGROUND: Persimmon (Diospyros kaki) is a familiar and widespread fruit, cultivated worldwide. To date, physiological and chemical changes in fermented persimmon fruit and its active compounds have been rarely investigated. Moreover, comparative studies on the pharmacological activities of fermented persimmon fruit-derived compounds have not been reported. RESULTS: To investigate the effect of traditional fermented foods on immunostimulatory activity, non-fermented persimmon fruit (D. kaki, DK) and fermented persimmon fruit (fermented D. kaki, FDK) were prepared and further fractionated into low- and high-molecular weight fractions. FDK exhibited significantly higher activity toward the production of macrophage-stimulatory mediators compared with that of DK, and the high-molecular weight fraction (FDK-H) isolated from FDK was shown to have more potent activity than FDK. FDK-H not only increased the expression of immunostimulatory genes (TNF-α, IL-6, IL-12, and iNOS), but also stimulated the phosphorylation of both MAPK (ERK, JNK, and p38) and NF-κB (p65 and IκB) signaling molecules underlying macrophage activation. The putative chemical characteristic of FDK-H was identified as a pectic rhamnogalacturonan (RG) I-rich polysaccharide with a high molecular weight of 304 kDa containing galacturonic acid, arabinose, rhamnose, and galactose as the major monosaccharide units. CONCLUSION: The present study reveals that traditional fermentation is a useful method for increasing the macrophage-immunostimulatory activity of persimmon fruit, and the increased activity may be associated with structural modification of persimmon polysaccharides. This study may serve to identify a functional ingredient as an immunostimulatory agent, and our results may be applied to develop a new immunostimulatory product using FDK-H. © 2021 Society of Chemical Industry.


Asunto(s)
Diospyros , Diospyros/química , Frutas/química , Macrófagos , FN-kappa B/genética , Pectinas , Polisacáridos/química
17.
Biofabrication ; 14(1)2022 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-34933294

RESUMEN

As the myelin sheath is crucial for neuronal saltatory conduction, loss of myelin in the peripheral nervous system (PNS) leads to demyelinating neuropathies causing muscular atrophy, numbness, foot deformities and paralysis. Unfortunately, few interventions are available for such neuropathies, because previous pharmaceuticals have shown severe side effects and failed in clinical trials. Therefore, exploring new strategies to enhance PNS myelination is critical to provide solution for such intractable diseases. This study aimed to investigate the effectiveness of electrical stimulation (ES) to enhance myelination in the mouse dorsal root ganglion (DRG)-anex vivomodel of the PNS. Mouse embryonic DRGs were extracted at E13 and seeded onto Matrigel-coated surfaces. After sufficient growth and differentiation, screening was carried out by applying ES in the 1-100 Hz range at the beginning of the myelination process. DRG myelination was evaluated via immunostaining at the intermediate (19 daysin vitro(DIV)) and mature (30 DIV) stages. Further biochemical analyses were carried out by utilizing ribonucleic acid sequencing, quantitative polymerase chain reaction and biochemical assays at both intermediate and mature myelination stages. Imaging of DRG myelin lipids was carried out via time-of-flight secondary ion mass spectrometry (ToF-SIMS). With screening ES conditions, optimal condition was identified at 20 Hz, which enhanced the percentage of myelinated neurons and average myelin length not only at intermediate (129% and 61%) but also at mature (72% and 17%) myelination stages. Further biochemical analyses elucidated that ES promoted lipid biosynthesis in the DRG. ToF-SIMS imaging showed higher abundance of the structural lipids, cholesterol and sphingomyelin, in the myelin membrane. Therefore, promotion of lipid biosynthesis and higher abundance of myelin lipids led to ES-mediated myelination enhancement. Given that myelin lipid deficiency is culpable for most demyelinating PNS neuropathies, the results might pave a new way to treat such diseases via electroceuticals.


Asunto(s)
Ganglios Espinales , Células de Schwann , Animales , Células Cultivadas , Lípidos , Ratones , Vaina de Mielina/fisiología , Regulación hacia Arriba
18.
Korean J Fam Med ; 42(6): 413-424, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34871482

RESUMEN

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and "healthy aging" become more and more important, these guidelines are also expected to increase in clinical usefulness.

19.
Nutrients ; 13(11)2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34836040

RESUMEN

We investigated the association between dietary habits, evaluated using the modified Mini Dietary Assessment Index for Koreans (MDA), and lipid control among patients aged ≥20 years who had used pravastatin for dyslipidemia for 6 months. Participants were administered questionnaires regarding sociodemographic characteristics and lifestyle factors. Odds ratios and 95% confidence intervals for the control of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at 6 months for each category of the modified MDA items were calculated through multivariate logistic regression analysis. The odds for controlled LDL-C was higher among those who consumed cholesterol-rich foods <1 time/week (3.27, 1.25-8.57) than for those who did so ≥4 times/week. The odds for controlled TG was higher among those who always consumed dairy products (2.96, 1.36-6.44), ate protein-rich foods three times/day (2.94, 1.06-8.10), and had a regular eating schedule (3.02, 1.30-7.00) than among those who did not have any of these. The odds for controlled TC was higher among those with a regular eating schedule (3.47, 1.55-7.76) than among their counterparts. Patients with dyslipidemia should consume less cholesterols, consume more dairy and protein-rich foods, and follow a regular eating schedule to control lipid profiles.


Asunto(s)
Dieta/estadística & datos numéricos , Dislipidemias/sangre , Conducta Alimentaria/fisiología , Lípidos/sangre , Pravastatina/uso terapéutico , Anciano , Colesterol/sangre , LDL-Colesterol/sangre , Dieta/efectos adversos , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , República de Corea , Encuestas y Cuestionarios , Triglicéridos/sangre
20.
Molecules ; 26(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805791

RESUMEN

Persimmon (Diospyros kaki), a familiar and widespread fruit worldwide, is known to exhibit several physiological effects because of the presence of pharmacologically active compounds called phytochemicals. However, its high-molecular-weight compounds, particularly polysaccharides, have not been extensively studied. In this study, D. kaki extract (DK) was fractionated into low- and high-molecular-weight fractions (DK-L and DK-H, respectively) through ethanol fractionation, and their effects on antioxidant, anti-inflammatory, and antiwrinkle activities were investigated by an in vitro system. DK-H contained significantly higher contents of neutral sugar, uronic acid, and polyphenols compared to DK and DK-L. Furthermore, DK-H exhibited significantly improved pharmacological activities, such as antioxidant, anti-inflammatory, and antiwrinkle properties, compared to those of DK and DK-L, demonstrating that DK-H may play an important role in mediating the beneficial effects of persimmon. Sugar composition analysis and molecular characterization indicated that DK-H consisted of a galacturonic acid (GalA)-rich polysaccharide with a molecular weight of >345 kDa that mainly comprised GalA and small amounts of neutral sugar and polyphenol residues. These results suggest that the bioactive fraction DK-H is likely to be a GalA-rich pectic polysaccharide containing a small number of polyphenol residues, which may be a novel candidate in the pharmaceutical and cosmeceutical industries.


Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Diospyros/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Animales , Antiinflamatorios/química , Antioxidantes/química , Línea Celular , Humanos , Técnicas In Vitro , Ratones , Peso Molecular , Elastasa Pancreática/antagonistas & inhibidores , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Polisacáridos/química , Células RAW 264.7 , República de Corea
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